Three undescribed dihydrostilbene glycosides from leaves of Camellia oleifera Abel. And their anti-inflammatory activity.

Three previously unidentified dihydrostilbene glycosides, named oleiferaside A (1), oleiferaside B (2), and oleiferaside C (3), were discovered through a phytochemical exploration on Camellia oleifera Abel. leaves. Additionally, nine known secondary metabolites (4-12) were also identified. The undescribed secondary metabolites 1-3 were elucidated as 3,5-dimethoxydihydrostilbene 4'-O-α-l-arabinofuranosyl-(1 â†’ 6)-ß-d- glucopyranoside, 3,5-dimethoxydihydrostilbene 4'-O-α-l-arabinopyranosyl-(1 â†’ 6)-ß-d- glucopyranoside and 3,5-dimethoxydihydrostilbene 4'-O-ß-d-apiofuranosyl-(1 â†’ 6)-ß-d- glucopyranoside, respectively. HR-MS and NMR spectroscopy were utilized for determining the structures of the isolates. The natural products were assessed for their anti-inflammatory effect using RAW264.7 macrophage stimulated by LPS. The findings demonstrated that compounds 1-4 exhibited inhibitory activities on NO and PGE2 production without causing cytotoxicity. These observations suggest that these compounds may have potential anti-inflammatory properties.

NTPDase1-ATP-P2Y2Rs axis in the sciatic nerve contributes to acupuncture at "Zusanli" (ST36)-induced analgesia in ankle arthritis rats.

BACKGROUND: The efficacy of acupuncture at Zusanli (ST36) in alleviating lower-limb pain is widely acknowledged in clinical practice, while its underlying mechanism remains incompletely elucidated. Our previous research had revealed that the prompt analgesia induced by needling-ST36 was accompanied by expression alterations in certain exco-nucleotidases within the sciatic nerve. Building upon this finding, the current work focused on NTPDase1, the primary ecto-nucleotidase in the human body, which converts ATP into AMP. METHODS: A 20-min acupuncture was administered unilaterally at the ST36 on rats with acute ankle arthritis. The pain thresholds of the injured hind paws were determined. Pharmacological interference was carried out by introducing the corresponding reagents to the sciatic nerve. ATP levels around the excised nerve were measured using a luciferase-luciferin assay. Live calcium imaging, utilizing the Fura 2-related-F340/F380 ratio, was conducted on Schwann cells in excised nerves and cultured rat SCs line, RSC96 cells. RESULTS: The analgesic effect induced by needling-ST36 was impaired when preventing ATP degradation via inhibiting NTPDase1 activities with ARL67156 or Ticlopidine. Conversely, increasing NTPDase1 activities with Apyrase duplicated the acupuncture effect. Similarly, preventing the conversion of AMP to adenosine via suppression of NT5E with AMP-CP hindered the acupuncture effect. Unexpectedly, impeded ATP hydrolysis ability and diminished NTPDase1 expression were observed in the treated group. Agonism at P2Y2Rs with ATP, UTP, or INS365 resulted in anti-nociception. Contrarily, antagonism at P2Y2Rs with Suramin or AR-C 118925xx prevented acupuncture analgesia. Immunofluorescent labeling demonstrated that the treated rats expressed more P2Y2Rs that were predominant in Schwann cells. Suppression of Schwann cells by inhibiting ErbB receptors also prevented acupuncture analgesia. Finally, living imaging on the excised nerves or RSC96 cells showed that agonism at P2Y2Rs indeed led to [Ca2+]i rise. CONCLUSION: These findings strongly suggest that the analgesic mechanism of needling-ST36 on the hypersensation in the lower limb partially relies on NTPDase1 activities in the sciatic nerve. In addition to facilitating adenosine signaling in conjunction with NT5E, most importantly, NTPDase1 may provide an appropriate low-level ATP milieu for the activation of P2Y2R in the sciatic nerve, particularly in Schwann cells.

Phytochemical constituents from rhizomes of Dryopteris crassirhizoma and their anti-inflammatory activity.

The phytochemical investigation on the rhizomes of Dryopteris crassirhizoma (Dryopteridaceae) resulted in the discovery of one novel compound, drycrassirhizomamide A (1), and one new natural product, drycrassirhizomamide B (2), as well as four known isolates, (S)-(-)-N-benzoylphenylalaninol (3), blumenol A (4), 8-C-glucosylnoreugenin (5), and dryopteroside (6). Their chemical structures were identified by NMR and mass spectroscopy. Compounds 1-2 were determined to be 1,19-diethyl 10-oxo-2,9,11,18-tetraazanonadecanedioate and C,C'-diethyl N,N'-1,6-hexanediylbis[carbamate]. The anti-inflammatory activities of these compounds were evaluated with LPS-stimulated RAW264.7 macrophage and BV2 microglia. The results showed that compounds 1-3 and 6 have inhibitory effects of NO production with IC50 values of 13.41, 30.36, 25.51, and 11.35 µM in LPS-stimulated RAW264.7 cells. Also, compounds 1 and 4-6 have abilities to inhibit NO production with the IC50 values of 40.11, 30.94, 15.76, and 16.79 µM in BV2 cells, which demonstrated that they may possess the potential anti-inflammatory activity.

[Mechanism of Danggui Sini Decoction in improving kidney injury caused by blood stasis syndrome based on metabolomics and network pharmacology].

This article analyzed the mechanism of Danggui Sini Decoction(DSD) in improving kidney injury caused by blood stasis syndrome(BSS) in rats. Firstly, 32 female SD rats were randomly divided into the following four groups: a normal group and a BSS group, both receiving an equal amount of distilled water by gavage; a normal+DSD group and a BSS+DSD group, both receiving 5.103 g·kg~(-1) DSD orally for a total of 14 days. Daily cold water bath was given to establish the BSS model, and on the 14th day, BSS rats were subcutaneously injected with 0.8 mg·kg~(-1) adrenaline. Normal rats were subjected to the water bath at 37 ℃ and injected with an equal volume of distilled water. After the experiment, 24-hour urine, serum, and kidney samples were collected for metabolomic analysis, biochemical measurements, and hematoxylin-eosin(HE) staining. The study then employed ~1H-NMR metabolomic technology to reveal the metabolic network regulated by DSD in improving BSS-induced kidney injury and used network pharmacology to preliminarily elucidate the key targets of the effectiveness of DSD. Pathological and biochemical analysis showed that DSD intervention significantly reduced inflammation and abnormal levels of blood creatinine, blood urea nitrogen, and urine protein in the kidneys. Metabolomic analysis indicated that DSD attenuated BSS-induced kidney injury primarily by regulating 10 differential metabolites and three major metabolic pathways(taurine and hypotaurine metabolism, citrate cycle, and acetaldehyde and dicarboxylic acid metabolism). Network pharmacology analysis suggested that the protective effect of DSD against BSS-induced kidney injury might be related to two key genes, ATP citrate lyase(ACLY) and nitric oxide synthase 2(NOS2), and two main metabolic pathways, i.e., arginine biosynthesis, and arginine and proline metabolism. This study, from the perspective of network regulation, provides initial insights and evidence into the mechanism of DSD in improving kidney injury induced by BSS, offering a basis for further investigation into the molecular mechanisms underlying its efficacy.

Causal relationship between genetically predicted depression and cancer risk: a two-sample bi-directional mendelian randomization.

BACKGROUND: Depression has been reported to be associated with some types of cancer in observational studies. However, the direction and magnitude of the causal relationships between depression and different types of cancer remain unclear. METHODS: We performed the two-sample bi-directional mendelian randomization with the publicly available GWAS summary statistics to investigate the causal relationship between the genetically predicted depression and the risk of multiple types of cancers, including ovarian cancer, breast cancer, lung cancer, glioma, pancreatic cancer, lymphoma, colorectal cancer, thyroid cancer, bladder cancer, and kidney cancer. The total sample size varies from 504,034 to 729,150. Causal estimate was calculated by inverse variance weighted method. We also performed additional sensitivity tests to evaluate the validity of the causal relationship. RESULTS: After correction for heterogeneity and horizontal pleiotropy, we only detected suggestive evidence for the causality of genetically predicted depression on breast cancer (OR = 1.09, 95% CI: 1.03-1.15, P = 0.0022). The causal effect of depression on breast cancer was consistent in direction and magnitude in the sensitivity analysis. No evidence of causal effects of depression on other types of cancer and reverse causality was detected. CONCLUSIONS: The result of this study suggests a causative effect of genetically predicted depression on specific type of cancer. Our findings emphasize the importance of depression in the prevention and treatment of breast cancer.

Painful Diabetic Neuropathy Is Associated with Compromised Microglial IGF-1 Signaling Which Can Be Rescued by Green Tea Polyphenol EGCG in Mice.

Background: Painful diabetic neuropathy (PDN) is a frequent and troublesome complication of diabetes, with little effective treatment. PDN is characterized by specific spinal microglia-mediated neuroinflammation. Insulin-like growth factor 1 (IGF-1) primarily derives from microglia in the brain and serves a vital role in averting the microglial transition into the proinflammatory M1 phenotype. Given that epigallocatechin-3-gallate (EGCG) is a potent anti-inflammatory agent that can regulate IGF-1 signaling, we speculated that EGCG administration might reduce spinal microglia-related neuroinflammation and combat the development of PDN through IGF-1/IGF1R signaling. Methods: Type 1 diabetes mellitus (T1DM) was established by a single intraperitoneal (i.p.) injection of streptozotocin (STZ) in mice. The protein expression level of IGF-1, its receptor IGF1R, interleukin 1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) was determined by Western blot or immunofluorescence. Results: The spinal IGF-1 expression markedly decreased along with the presence of pain-like behaviors, the spinal genesis of neuroinflammation (increased IL-1ß, TNF-α, and Iba-1+ microglia), and the intensified M1 microglia polarization (increased iNOS+Iba-1+ microglia) in diabetic mice. IGF-1 could colocalize with neurons, astrocytes, and microglia, but only microglial IGF-1 was repressed in T1DM mice. Furthermore, we found that i.t. administration of mouse recombinant IGF-1 (rIGF-1) as well as i.t. or i.p. treatment with EGCG alleviated the diabetes-induced pain-like behaviors, reduced neuroinflammation (suppressed IL-1ß, TNF-α, and Iba-1+ microglia), prevented the M1 microglia polarization (less iNOS+Iba-1+ microglia), and restored the microglial IGF-1 expression. Conclusions: Our data highlighted the importance of maintaining spinal IGF-1 signaling in treating microglia-related neuroinflammation in PDN. This study also provides novel insights into the neuroprotective mechanisms of EGCG against neuropathic pain and neuroinflammation through IGF-1 signaling, indicating that this agent may be a promising treatment for PDN in the clinical setting.

Identifying optimal clinical trial candidates for locoregionally advanced nasopharyngeal carcinoma: Analysis of 9468 real-world cases and validation by two phase 3 multicentre, randomised controlled trial.

BACKGROUND AND PURPOSE: This study aims to identify the optimal high-risk candidates for clinical trials in locoregionally advanced nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Non-metastatic NPC patients (n = 9,468) were included. Recursive partitioning analyses (RPA) were performed to generate risk stratification. Receiver operating characteristics curve was used to determine the cut-off value of pre-treatment Epstein-Barr virus (EBV) DNA for progression-free survival (PFS). Individual-level data from two clinical trials were used for validation. RESULTS: Anatomic stratification based on T and N category (eighth edition TNM, TNM-8) classified the N2-3 or T4 as an anatomic high-risk group with 5-year PFS of 69% (95% confidence interval: 68-71%). Prognostic stratification identified patients with pre-treatment EBV DNA ≥4000 copies/mL as a prognostic high-risk group with 5-year PFS of 69% (67-70%). The c-index was significantly higher for anatomic stratification (0.621, p < 0.001) and prognostic stratification (0.585, p < 0.001) compared with existing TNM-8 stage groups (0.562). The validation cohorts based on clinical trials data showed greater PFS benefit than the results of the original trials [Hazard ratio: NCT01245959, 0.64 vs. 0.67; NCT01872962, 0.42 vs. 0.52]. Moreover, detectable post-treatment EBV DNA indicated a high risk of progression with 5-year PFS of 38.7% and was the most adverse independent factor for all endpoints. CONCLUSIONS: N2-3 or T4 NPC patients were ideal candidates for multicenter clinical trials in locoregionally advanced NPC. Patients with detectable post-treatment EBV DNA are suitable candidates for adjuvant trials.

Progression-free survival assessed per immune-related or conventional response criteria, which is the better surrogate endpoint for overall survival in trials of immune-checkpoint inhibitors in lung cancer: A systematic review and meta-analysis.

Progression-free survival (PFS) has been used as a surrogate endpoint for overall survival (OS) in lung cancer trials. The pattern of response to immune-checkpoint inhibitors (ICIs) differs from that to conventional chemotherapy, so immune-related response evaluation criteria were proposed. This study aims at determining which PFS measure, PFS assessed per immune-related response evaluation criteria (iPFS), or conventional criteria (cPFS), is the better surrogate endpoint for OS in trials of ICIs in lung cancer. We selected clinical trials in lung cancer that administered ICIs to at least one arm and reported both median OS and median PFS from PubMed, Embase, and The Cochrane Library. We compared the correlation between treatment effect (hazard ratio) on OS and cPFS or iPFS and the correlation between median OS and median cPFS or iPFS using weighted linear regression at trial level. We analyzed 78 ICI arms (13,438 patients) from 54 studies, including 66 arms with cPFS, seven arms with iPFS, and five arms with both kinds of PFS. We demonstrated an excellent correlation between treatment effect (hazard ratio) on OS and iPFS (RWLS2  = 0.91), while the correlation was moderate for cPFS (RWLS2  = 0.38). Similarly, the correlation between median OS and median iPFS was also strong (RWLS2 ranging from 0.86 to 0.96) across different phases of trials and different types of lung cancer, ICI, and treatment modalities, while it was much weaker for median cPFS (RWLS2 ranging from 0.28 to 0.88). In conclusion, iPFS provides better trial-level surrogacy for OS than cPFS in trials of ICIs in lung cancer.

Acanthopanax henryi: Review of Botany, Phytochemistry and Pharmacology.

Acanthopanax henryi (Oliv.) Harms (Araliaceae), also known as Eleutherococcus henryi and Caoyewujia (Hengliwujia) in Chinese, is a widely used traditional Chinese herb with the effects of expelling wind and removing dampness, relaxing the muscles and stimulating the blood circulation, and regulating the flow of qi to alleviate pain in the theory of Traditional Chinese Medicine. Acanthopanax henryi (AH, thereafter) possesses ginseng-like activities and is known as ginseng-like herb. In the past decade, a great number of phytochemical and pharmacological studies on AH have been carried out. Several kinds of chemical compositions have been reported, including terpenoids (monoterpenoids, diterpenoids, and triterpenoid saponins), phenylpropanoids, caffeoyl quinic acid derivatives, flavonoids, lignans, sterols, fatty acids, etc., among which, triterpenoid saponins were considered to be the most active components. Considerable pharmacological experiments in vitro have demonstrated that AH possessed anti-neuroinflammatory, anti-adipogenic, anti-inflammatory, antibacterial, anti-cancer, anti-oxidation, anti-AChE, anti-BuChE, and antihyaluronidase activities. The present review is an up-to-date and comprehensive analysis of the botany, phytochemistry, and pharmacology of AH.

Serum metabolic profiling of traditional Chinese medicine syndromes in patients with diarrhea-predominant irritable bowel syndrome.

OBJECTIVE: The clinical symptoms of diarrhea-predominant irritable bowel syndrome (IBS-D) can be effectively improved by traditional Chinese medicine (TCM) treatment, based on the usage of specific therapies for different TCM syndromes. However, in the stage of diagnosis, the standard criteria for the classification of TCM syndrome were still deficient. Through serum metabolic profiling, this study aimed to explore potential biomarkers in IBS-D patients with different TCM syndromes, which can assist in diagnosis of the disease. METHODS: Serum samples were collected from healthy controls (30 cases), IBS-D patients with Liver-Stagnation and Spleen-Deficiency syndrome (LSSD, 30 cases), Yang Deficiency of Spleen and Kidney syndrome (YDSK, 11 cases) and Damp Abundance due to Spleen-Deficiency syndrome (DASD, 22 cases). Serum metabolic profiling was conducted by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The potential biomarkers were screened by orthogonal partial least square-discriminate analysis, while metabolic pathways undergoing alterations were identified by pathway enrichment analysis in MetaboAnalyst 4.0. RESULTS: Overall, 34 potential biomarkers were identified in LSSD group, 36 in YDSK group and 31 in DASD group. And the 13 metabolites shared by three groups were determined as the potential biomarkers of IBS-D. Glycerophospholipid metabolism was disturbed significantly in IBS-D patients, which may play a role in IBS-D through inflammation. What's more, three TCM syndromes have the specific potential biomarkers in glycerophospholipid metabolism. CONCLUSION: The serum metabolomics revealed that different TCM syndrome types in IBS-D may have different metabolic patterns during disease progression and glycerophospholipid metabolism was one of the pathways, whose metabolism was disturbed differently among three TCM syndromes in IBS-D. Therefore, the specific potential biomarkers in glycerophospholipid metabolism of three TCM syndromes in IBS-D can serve as the objective indicators, which can facilitate the TCM-syndrome objective classification of IBS-D.

Evolving landscape and academic attitudes toward the controversies of global immuno-oncology trials.

This cross-sectional and longitudinal descriptive analysis aimed to track the evolving landscape of global immuno-oncology (IO) trials and provide insight into the resolution of IO-related controversies. Clinical trials (n = 4510) registered on ClinicalTrials.gov in 2007 to 2019 studying immune checkpoint inhibitors (ICIs), adoptive cell transfer (ACT), cancer vaccines and immune modulators were included. Most of IO trials are Phase 2 and focus on ICIs and multiple IO therapies. The United States leads global IO research, with stable growth and the best methodological quality. Mainland China ranks first in the number of ACT trials but has the lowest article publication rate (6.2%). A multiple-arm comparative design is often adopted in multiple IO therapies trials (44.0%). Trials studying ICIs and multiple IO therapies are likely to use early registration (80.0% and 86.6%) and stringent corticosteroid-/infection-related criteria. Hospitals have provided the most extensive and strongest support for all IO categories. Big pharma prefers to fund Phase 3-4 ICI trials (6.98%), while small pharma has a wider sponsorship favoring Phase 1-2 trials. The "partial-use-of-corticosteroids" strategy is generally well accepted in ICI trials with a definitive trend (32.5%; P < .001) but is associated with the poor dissemination of results (P ≤ .020), while the complete disclosure and standardization of dose/timing limits are still lacking. Disparities in design features and dissemination of results are widespread in IO trials and are modulated by IO category, cancer type and sponsor. We propose policy reforms to redefine the timely publication of IO trials and standardize the resolution of corticosteroid-/infection-related issues.

Sintilimab-Induced Myocarditis Overlapping Myositis in a Patient With Metastatic Thymoma: A Case Report.

Although immune checkpoint inhibitor (ICI)-related myocarditis has been widely discussed, a lot of gaps and challenges in its clinical course and rational intervention remain elusive. We present the case of a 33-year-old man with a history of metastatic thymoma who developed dyspnea and muscle weakness 1 month after the first dose of sintilimab. He was asymptomatic but found to have a mild elevation of troponin-T and a moderate increase of creatine kinase 20 days after the infusion. Although the scheduled second dose was deferred, he developed dyspnea, left bundle branch block, and left ventricular enlargement that is suggestive of Grade 3 ICI-related myocarditis, complicated with myositis/myasthenia gravis 10 days later. Fortunately, his response to intensive immunosuppressive therapy was good.

The Pattern of Time to Onset and Resolution of Immune-Related Adverse Events Caused by Immune Checkpoint Inhibitors in Cancer: A Pooled Analysis of 23 Clinical Trials and 8,436 Patients.

PURPOSE: The occurrence pattern of immune-related adverse events (irAEs) induced by immune checkpoint inhibitor (ICI) in cancer treatment remains unclear. MATERIALS AND METHODS: Phase II-III clinical trials that evaluated ICI-based treatments in cancer and were published between January 2007 and December 2019 were retrieved from public electronic databases. The pooled median time to onset (PMT-O), resolution (PMT-R), and immune-modulation resolution (PMT-IMR) of irAEs were generated using the metamedian package of R software. RESULTS: Twenty-two eligible studies involving 23 clinical trials and 8,436 patients were included. The PMT-O of all-grade irAEs ranged from 2.2 to 14.8 weeks, with the longest in renal events. The PMT-O of grade ≥ 3 irAEs was significantly longer than that of all-grade irAEs induced by programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) inhibitors (27.5 weeks vs. 8.4 weeks, p < 0.001) and treatment of nivolumab (NIV) plus ipilimumab (IPI) (7.9 weeks vs. 6.0 weeks, p < 0.001). The PMT-R of all-grade irAEs ranged from 0.1 to 54.3 weeks, with the shortest and longest in hypersensitivity/infusion reaction and endocrine events, respectively. The PMT-IMR of grade ≥ 3 irAEs was significantly shorter than that of all-grade irAEs caused by PD-1/PD-L1 blockade (6.9 weeks vs. 40.6 weeks, p=0.002) and NIV+IPI treatment (3.1 weeks vs. 5.9 weeks, p=0.031). CONCLUSION: This study revealed the general and specific occurrence pattern of ICI-induced irAEs in pan-cancers, which was deemed to aid the comprehensive understanding, timely detection, and effective management of ICI-induced irAEs.

Association between outcome disparities and pragmatic features related to clinical trial and real-world settings in nasopharyngeal carcinoma: A population-based retrospective cohort study, 2006-2016.

BACKGROUND: Prognosis often differs between trial participants and nontrial (pragmatic) patients in similar clinical scenarios, raising a concern that results of trials may not represent those in real-world practice. METHODS AND MATERIALS: Individual patient data were extracted from three phase III randomized controlled trials and a big-data real-world database (n = 10,126). Patients with nasopharyngeal carcinoma receiving concurrent chemoradiotherapy (CCRT [control]: 2438 vs. 519) or induction chemotherapy plus CCRT (experimental) were included. Propensity score matching and correspondence analysis were used for data mining. RESULTS: Compared with the real-world CCRT cohort, clinical trials preferred to include cases with T4 (25.3-43.3% vs. 18.8%) and N2 (44.4-60.7% vs. 38.9%) categories. Real-world patients were more likely to undergo shorter irradiation time (44 vs. 46-49 days), inadequate chemotherapy cycles (70.6% vs. 25.2-43.9%), other chemotherapy (36.4% vs. 0.0%), and flexible regimens (≥3 vs. 1). Although real-world patients had better survival than trial participants, the survival disparities disappeared in the matched cohorts, except for in one trial with the lowest pragmatism assessment caused by stringent eligibility criteria and low flexibility of delivery. Stage specification, year of treatment, and Epstein-Barr virus DNA were related to survival disparities (all P ≤ 0.034). The influence of pragmatic features on survival mainly affected the control (all P ≤ 0.043) rather than the experimental group. CONCLUSION: Special attention should be paid to the control group when interpreting trial results. Assessing whether the pragmatic features of studies deviate from routine practice will lead to better conversion of trial findings into clinical guidelines.

The evolution of the nasopharyngeal carcinoma staging system over a 10-year period: implications for future revisions.

BACKGROUND: The classification criteria and staging groups for nasopharyngeal carcinoma described in the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system have been revised over time. This study assessed the proportion of patients whose staging and treatment strategy have changed due to revisions of the UICC/AJCC staging system over the past 10 years (ie, from the sixth edition to the eighth edition), to provide information for further refinement. METHODS: We retrospectively reviewed 1901 patients with non-metastatic nasopharyngeal carcinoma treated in our cancer center between November 2009 and June 2012. The Akaike information criterion and Harrell concordance index were applied to evaluate the performance of the staging system. RESULTS: In total, 25 (1.3%) of the 1901 patients who were staged as T2a according to the sixth edition system were downgraded to T1 in the eighth edition; 430 (22.6%) staged as N0 in the sixth edition were upgraded to N1 in the eighth edition; 106 (5.6%) staged as N1/2 in the sixth edition were upgraded to N3 in the eighth edition. In addition, 51 (2.7%) and 25 (1.3%) of the study population were upstaged from stage I to stage II and stage II to stage IVa, respectively; 10 (0.5%) was downgraded from stage II to stage I. The survival curves of adjacent N categories and staging groups defined by eighth classification system were well-separated. However, there was no significant difference in the locoregional failure-free survival (P = 0.730) and disease-free survival (P = 0.690) rates between the T2 and T3 categories in the eighth edition classification system. CONCLUSIONS: Modifications to the tumor-node-metastasis staging system over the past 10 years have resulted in N classification changes in numerous cases. Although the eighth edition tumor-node-metastasis staging system better predicts survival outcomes, the T classification could be simplified in future revisions.

Induction versus adjuvant chemotherapy combined with concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: A propensity score-matched analysis.

OBJECTIVES: To explore the role of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) and CCRT plus adjuvant chemotherapy (AC) in locoregionally advanced nasopharyngeal carcinoma (LANPC). MATERIALS AND METHODS: The propensity score-matched (PSM) method was adopted to balance variables. We identified independent prognostic factors using Cox regression analysis and compared outcomes between two chemotherapy treatment combinations for patients in different subgroups. RESULTS: A total of 550 patients were selected by one-to-two PSM. Survival outcomes for the matched data set indicated that the IC + CCRT group achieved higher 5-year overall survival (OS; 89.3% vs 85.3%, P = 0.119), failure-free survival (FFS; 80.2% vs 79.0%, P = 0.722) and distant metastasis-free survival (DMFS; 87.4% vs 84.4%, P = 0.322) compared with CCRT + AC, although this was statistically non-significant. Subgroup analysis revealed that IC + CCRT was associated with significantly improved OS (Hazard ratio [HR] = 2.68, 95% Confidence interval [CI] = 1.16-6.22, P = 0.017), FFS (HR = 1.94, 95% CI = 1.06-3.57, P = 0.029) and locoregional relapse-free survival (LRRFS; HR = 2.63, 95% CI = 1.04-6.68, P = 0.034) in T3 disease. Moreover, this combination of treatment could significantly prolong OS (HR = 3.72, 95% CI = 1.41-9.80, P = 0.004) in N2 disease. However, the superiority of CCRT + AC was only observed in LRRFS (HR = 0.18, 95% CI 0.04-0.79, P = 0.010) for the T4 subgroup. CONCLUSION: IC + CCRT should be strongly considered by patients with LANPC, especially those with T3 or N2 disease.